1. AP Biology Chapter 11 Lecture Notes Cell Communication

2. Evolution of Cell Signaling Signal transduction pathway: series of steps by which a signal on a cell’s surface is converted into a specific cellular response –Pathway similarities suggest ancestral signaling molecules evolved in prokaryotes and modified later in eukaryotes –Concentration of signaling molecules allows bacteria to detect population density (quorum sensing) may form  biofilms

3. Local and Long-Distance Signaling Cells in multicellular organisms communicate via chemical messengers Animal and plant cells have cell junctions that directly connect cytoplasm of adjacent cells –Gap junctions –Plasmodesmata Contact-Dependent: animal cells may communicate by direct contact (cell-cell recognition) –Immune Response In other cases, animal cells communicate using messenger molecules that travel only short distances –Paracrine signals (example: growth factors) –Neurotransmitters In long-distance signaling, plants and animals use chemicals called hormones (endocrine signals)    

4. Three Stages of Cell Signaling Cells receiving signals go through 3 processes: –Reception –Transduction –Response Animation: Overview of Cell Signaling Animation: Overview of Cell Signaling EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response TransductionResponse 2 3 Reception 1

5. Reception: Signal Molecule Binds to a Receptor Protein, Causing it to Change Shape Most receptors are membrane proteins b/c most signal molecules are very polar and can’t pass through membrane 3 types of membrane receptors: –G protein-coupled receptors (C) –Receptor tyrosine kinases (B) –Ion channel receptors (A) Another type of receptor is intracellular (D) Binding between signal molecule (ligand) and receptor is highly specific Shape change in receptor is often initial transduction of signal

6. G protein-coupled receptor: –Plasma membrane receptor that works with help of a G protein (a peripheral protein) –Acts as On/off Switch: If GDP is bound to the G protein, the G protein is inactive –Many medications affect cells in this manner G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme 1 2 3 4 G Protein Animation

7. Receptor tyrosine kinases (enzymes) –Membrane receptors attach phosphates to tyrosines (peripheral proteins) –Can trigger (On/off switch) multiple signal transduction pathways at once Signaling molecule (ligand) Ligand-binding site Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P 1 2 34 Tyrosine Kinase (Enzyme) Animation

8. Ligand-gated Ion Channel Receptor: – acts as a gate when receptor changes shape –allows ions, such as Na + or Ca 2+, through a channel in the receptor –Important in neurons Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1 Ion Channel Animation

9. Intracellular Receptors Found in cytosol or nucleus of target cells Small hydrophobic chemical messengers (i.e. steroid and thyroid hormones) readily cross membrane and activate receptors Activated hormone- receptor complex can act as a transcription factor, turning on specific genes Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM Intracellular Receptors and Transcription Video

11. Transduction: Cascades of Molecular Interactions that Relay Signals from Receptors to Target Molecules in the Cell Signal transduction usually involves multiple steps Multistep pathways can amplify a signal Multistep pathways provide more opportunities for coordination and regulation of the cellular response The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, one receptor activates a protein, which activates another, and so on, until the the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein

12. Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to a protein (phosphorylation) Protein phosphatases remove phosphates from proteins (dephosphorylation) Phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on/off Amplification of Signals Video

13. Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i

14. Comprehension Check Indicate where each of the labels should appear in the figure. Receptor Relay molecules Transduction Activation of cellular response Signaling molecule Response Reception Receptor Relay Molecules Transduction Activation of Cellular Response Signaling Molecule ResponseReception

15. Small Molecules and Ions as Second Messengers The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger” Second messengers: small, nonprotein, water- soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases (not needed for ligand- gated ions) Cyclic AMP and calcium ions are common second messengers Animation: Signal Transduction Pathways Animation: Signal Transduction Pathways Second Messengers Video

16. First messenger Fig. 11-11 G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses

17. Fig. 11-13-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Various proteins activated Cellular responses Ca 2+ (second messenger) GTP

18. Response: Cell Signaling Leads to Regulation of Transcription or Cytoplasmic Activities Ultimately, signal transduction pathway leads to regulation of cell activities Cell’s response to extracellular signal is called “output response” may occur in cytoplasm or involve action in nucleus Many signaling pathways regulate synthesis of enzymes or other proteins, usually by turning genes on/off in nucleus –Final activated molecule may function as transcription factor Other pathways regulate the activity of enzymes Signaling pathways can also affect physical characteristics of cell, for example, cell shape/cell movement

19. Termination of the Signal Inactivation mechanisms are essential to cell signaling Occurs when signal molecules leave the receptor and the receptor reverts to its inactive state

20. Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis: programmed or controlled cell suicide –Cell is chopped and packaged into vesicles that are digested by scavenger cells –Prevents enzymes from leaking out of a dying cell and damaging neighboring cells –Important during embryonic development Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Death- signaling molecule Other proteases Active Ced-4 Active Ced-3 Nucleases Activation cascade (b) Death signal

21. Comprehension Check Which of the following best describes a signal transduction pathway? A. binding of a signal molecule to a cell protein B. catalysis mediated by an enzyme C. sequence of changes in a series of molecules resulting in a response D. binding of a ligand on one side of a membrane that results in a change on the other side E. the cell’s detection of a chemical or mechanical stimulus

22. Comprehension Check A steroid hormone binds to an intracellular receptor. When it does, the resulting complex is able to do which of the following? Why? A. open channels in the membrane for other substances to enter B. open channels in the nuclear envelope for cytoplasmic molecules to enter C. mediate the transfer of phosphate groups to/from ATP D. act as a transcription factor in the nucleus E. make water-soluble molecules able to diffuse across membranes

23. Comprehension Check In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction? A. make functional ATP B. change a protein from its inactive to its active form C. change a protein from its active to its inactive form D. alter the permeability of the cell’s membranes E. produce an increase in the cell’s store of inorganic phosphates

24. Comprehension Check Which of the following is an example of signal amplification? A. catalysis of many cAMP molecules by several simultaneously binding signal molecules B. activation of 100 molecules by a single signal binding event C. activation of a specific gene by a growth factor D. activation of an enzyme molecule E. utilization of a second messenger system

25. Comprehension Check Which of the following is not a usual part of the process of apoptosis? A. cell shrinkage and blebbing B. destruction of the cell’s DNA C. formation of numerous vesicles to be digested D. damage to all cells in the immediate vicinity E. activation and deactivation of specific proteins